1. Nalley, Catlin

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New data from the landmark Phase III ASCENT study, which investigated sacituzumab govitecan versus single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC), were recently presented at the ESMO Congress 2021. This included an analysis examining health-related quality of life (Abstract 257P).

TNBC Patients. TNBC ... - Click to enlarge in new windowTNBC Patients. TNBC Patients

"Health-related quality of life (HRQoL) is a key outcome to assess the value of new anticancer treatments," noted study author Kevin Punie, MD, Medical Oncology, Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven in Belgium. "Especially in the incurable treatment setting, the evolution of HRQoL under a specific treatment is an important variable to evaluate the impact of the treatment's safety and efficacy on the global physical, mental, and social functioning as perceived by the patient.


"In an optimal situation, a new anticancer treatment does not only delay disease progression and/or death, but also improves or delays deterioration in global quality of life," he continued. "In the ASCENT trial, the main objective was to determine whether HRQoL was similar in patients receiving [sacituzumab govitecan] compared to those patients receiving treatment of physician's choice."


Study Details

In the ASCENT trial, patients with metastatic TNBC who received two or more prior systemic therapies-at least one for metastatic disease-were randomized to receive sacituzumab govitecan (10 mg/kg IV on Day 1 and 8, every 21 days) or a single-agent chemotherapy of physician's choice (capecitabine, eribulin, vinorelbine, or gemcitabine).


Researchers assessed HRQoL at baseline, on Day 1 of each cycle, and at the end of study treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), according to Punie.


"This questionnaire measures patient perceptions of their own physical, mental, and social health, which can be influenced by disease symptoms and side effects of treatment," he explained, while noting that the differences between treatment groups in mean changes from baseline were estimated using a statistical model that accounts for the baseline value and similarity in multiple measurements over time from the same patient by using on-treatment data for cycles 2-6.


This secondary analysis of HRQoL included 419 patients-236 received sacituzumab govitecan and 183 received physician's choice. The median age was 54 years, and the number of median prior regimens was four. Brain metastases were present in 11 percent of patients.


The researchers found that patients who received sacituzumab govitecan had significantly and meaningfully greater improvements compared with those who received physician's choice of chemotherapy in global health status (0.66 vs. -3.42; p<0.05), physical functioning (1.31 vs. -4.39; p<0.01), and emotional functioning (3.34 vs. -0.55; p<0.05), according to Punie.


"Patients receiving [sacituzumab govitecan] also experienced lower symptomatic impact of fatigue (1.97 vs. 7.13; p<0.05), pain (-8.93 vs. -1.89; p<0.01), dyspnea (-3.79 vs. 3.95; p<0.01), and insomnia (-4.69 vs. 0.34; p<0.05) when compared to patients who received standard chemotherapy in the control arm of the ASCENT trial," he reported.


Only diarrhea-a known side effect-was significantly and meaningfully worse with sacituzumab govitecan (14.07 vs. -1.27; p<0.01); however, Punie noted, this did not appear to translate to an adverse impact on patients' global health score or functioning.


"Next to these significant and meaningful improvements observed in linear analysis, also the time to first clinically meaningful deterioration of HRQoL was significantly longer with [sacituzumab govitecan] when compared to single-agent chemotherapy of physician's choice for several primary HRQoL domains such as physical functioning, fatigue, and pain," said Punie, who noted that this delay in decline of important disease-related symptoms, such as cancer pain, is of major importance when prioritizing treatments.


"Given the important delays in disease progression or death associated with [sacituzumab govitecan] in advanced TNBC, this treatment option was already considered a standard of care before the release of these data," he stated.


"However, these data are very important to reassure patients that the improvement in outcome seen with [sacituzumab govitecan] is not limited to measures of disease, but could also positively impact their global self-perceived functioning, avoiding decline in quality-of-life which is one of the most important treatment goals in the incurable setting."


Conclusions, Next Steps

These positive HRQoL results associated with sacituzumab govitecan treatment are expected to impact the value assessment of this treatment for patients with advanced TNBC, according to Punie.


"For example, in the ESMO-Magnitude of Clinical Benefit Scale, which is a dynamic tool to assess the magnitude of clinical benefit of cancer medicines, an improvement or delayed deterioration in global QoL results in an upgrading of the score," he explained. "As such, it is expected that these findings will result in an upgrading of the current score of [sacituzumab govitecan] to the maximum score of five."


A peer-reviewed publication of these data is currently underway, and HRQoL will continue to be monitored in other clinical trials evaluating sacituzumab govitecan in disease areas beyond TNBC, noted Punie.


"The results of this HRQoL analysis underline that treatment with [sacituzumab govitecan] does not only improve outcomes for patients with TNBC by delaying disease progression and death, but is also associated with significant and clinically relevant improvements in HRQoL when compared to the quality-of-life evolution under treatment with standard chemotherapy," he explained. "These data further support the use of [sacituzumab govitecan] in patients with advanced TNBC who have received two prior chemotherapy regimens, at least one in the advanced setting."


Catlin Nalley is a contributing writer.